Safety and efficacy of increasing dosages of glycyl-glutamine for total parenteral nutrition in polytrauma patients.

Supplementation of parenteral nutrition with glutamine (GLN) has been suggested to improve the efficacy of nutritional support by stimulating protein synthesis and improving immunocompetence. In the present study we investigated the impact of infusing the dipeptide glycyl-glutamine (GLY-GLN) at increasing dosages on plasma amino acid concentrations in patients with polytrauma. Nine polytraumatized patients were randomly assigned according their age and their trauma score to three experimental groups. Group 1 received 280, group II 450, and group III 570 mg GLY-GLN per kg body weight/day for a period of four days (3rd to 7th posttraumatic day), resulting in a maximum daily GLN administration (calculated for a 70 kg patient) of 14 g, 21 g and 28 g, respectively. Seven polytraumatized patients receiving the nutrition solution without GLY-GLN supplementation served as controls. All patients received total parenteral nutrition with an average amino acid administration of 1.1 g/kg/day and a total energy intake of 30 kcal/kg/day. GLY-GLN infusion did not evoke any side effects. In comparison with the control group, arterial plasma GLN concentrations increased significantly on day I after start of infusion in groups II and III, but remained raised throughout the study period only in group III (p < 0.003). Similarly, plasma GLY concentrations were also significantly raised in group III (p < 0.04). The maximum increase of plasma GLY was found on the second infusion day, after which plasma concentrations of GLY fell to concentrations even below those observed in the control group at the end of the study period. Excretion of GLY-GLN, GLN or GLY in the urine during the GLY-GLN infusions was negligible. We conclude from this first available dose finding study on glutamine-containing dipeptides that in polytraumatized patients infusion of 570 mg/kg/day of GLY-GLN (corresponding to 28 g glutamine or 40 g dipeptide/70 kg, respectively) is necessary to induce a sustained effect on plasma glutamine concentrations. No pathological accumulation of free glycine or of the dipeptide was seen with any of the three dosage steps of GLY-GLN. Thus, the administration of even high doses of GLY-GLN is feasible and safe in patients with polytrauma and is not associated with any relevant renal substrate loss.